There is a lack of knowledge regarding genetic diseases and its prevention among general population an important premise is that a better understanding of the genetic etiology of the diseases can facilitate early detection in high risk subjects. It also helps in designing more effective intervention strategies. Exciting new technology based on the foundation of genetic research has the potential to further enhance the quality of life. Progress in the field will require training of a new generation of the scientists with requisite skills, as well as greater collaboration and interdisciplinary work. The traditional epidemiologic approach has proved useful for generating hypotheses and unraveling disease etiologies. But now it is possible to go beyond these methods and look inside the "black box" of the disease process which would be able to change the definition of the risk factors or clarify their location in the casual model.

Genetics is the branch of science concerned with the means and consequences of transmission and generation of the components of biological inheritance. Genetics is the study of genes, heredity, and genetic variation in living organisms. [1]

Gregor Johann Mendel an Augustinian priest and scientist and is referred as the "Father of genetics". [2] Mendel showed that the inheritance of traits follow particular laws, which were later named as Mendel's laws of inheritance. He studied segregation of traits in the garden pea (Pisumsativum) beginning in 1854 and presented his paper on "Experiments with Plant Hybridization" in 1866 and gave three laws of inheritance: Law of dominance, law of segregation and law of independent assortment. [3]

The behavior of genetic markers during the propagation of organisms follows a few simple rules where the genetic characters are discrete entities and their visible manifestations may be masked in some organisms, but the characters are nevertheless present. The presence of masked characters is revealed in subsequent generations, that is, they segregate in subsequent generations. Some pairs of genetic characters are linked, and the Pairs of linked characters can exchange partners, the process is referred as recombination. [4]

Studies of the degree of linkage of many pairs revealed a consistent linear relationship. [5],[6] This article will try to unify some of these discoveries into major findings [Table 1]. [7]

Cell growth, migration, and differentiation in oral mucosa tooth or other craniofacial structures are controlled by molecular signals that in turn are governed by the genetic constitution of an individual. These molecular signals are also responsible for maintenance of integrity and ageing process. [8],[9]

A genetic disease is any disease that is caused by an abnormality in an individual's genome. The abnormality can range from minuscule to major or from a discrete mutation in a single base in the DNA of a single gene to a gross chromosome abnormality involving the addition or subtraction of an entire chromosome or set of chromosomes.

Mutation is a permanent change in the sequence of DNA. In order for an observable effect, mutations must occur in gene exons or regulatory elements. Changes in the noncoding regions of DNA (introns and junk DNA) do not affect function. [10]

Mutations can be caused by external (exogenous) such as environmental factors such as sunlight, radiation, and smoking may induce mutations or endogenous (native) factors. Physical or chemical agents that induce mutations in DNA are called Mutagens and are said to be mutagenic. [11] The type of mutation in the germline is heritable example cancer family syndrome while somatic mutations occur in nongermline tissue and are nonheritable. [10],[11],[12]

Mutations can be advantageous and lead to an evolutionary advantage of a certain genotype. Mutations can also be deleterious, causing disease, developmental delays, structural abnormalities, or other effects. [11] Various kinds of mutations include Deletion, Frameshift Mutation, Insertion, Missense Mutation, Nonsense Mutation, Point Mutation, Silent Mutation, Splice Site Mutation, and Translocation. [12]

Genetic Disorders

Can be classified as single gene inheritance, multifactorial inheritance, chromosome abnormalities, and mitochondrial inheritance.

Single gene inheritance is also referred as Mendelian or monogenetic inheritance. This type of inheritance is caused by changes or mutations that occur in the DNA sequence of a single gene. They can be autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, or Y-linked. Some disorders including cystic fibrosis and sickle cell anemia are classical examples of single gene inheritance. [13]

Multifactorial inheritance or complex or polygenic inheritance is caused by a combination of environmental factors and mutations in multiple genes. Disorders like Alzheimer's disease and cancer are resultant of the multifactorial disorder. [14]

Chromosome abnormalities can occur due to a defective cell division leading to numerical abnormalities, or there may be structural abnormalities due to mutation. Numerical abnormalities can be due to autosomal aneuploidy resulting in disorders Trisomy 21 (Down syndrome),Trisomy 13 (Patau syndrome), and Trisomy 18 (Edward syndrome)and also due to sex chromosomal aneuploidy where there is addition and deletion of chromosomes in germ line cells, e.g., Kleinfelter syndrome (XXY) and Turner syndrome (45X). [15] Structural Abnormalities may be due to Chromosome Deletion (Cri-Du-Chat Syndrome), Chromosome Duplication in case of "Partial trisomy" or Chromosome Inversion which are not related to an increased risk of birth defects and/or developmental difficulties. [15]

The type of genetic disorder caused by mutations in the nonchromosomal DNA of mitochondria is referred as Mitochondrial Inheritance. An eye disease called Leber's hereditary optic atrophy and a form of dementia called MELAS (leading to mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) are certain diseases which are common examples of mitochondrial inheritance. [16][Table 2] represents genetic disorders affecting Oro-facial structures. [8],[17]

It refers to the study of the role of genetic factors in determining health and disease in families and interplay of such factors with environmental factors. This includes: [1]

Familial aggregation studies

Determines the genetic component of disease and relative contribution of genes and environment. Familial aggregation may result from shared genes, environmental exposures and similar socio-economic influences. It is used to determine the evidence for genetic factors in familial aggregation of a trait and when more formal genetic studies are required.

Segregation analysis

Determines the pattern of disease inheritance and evaluates the relative support for different transmission models for determining the transmission of a trait through families, by sequentially comparing models with each other. Investigators use segregation analyses to test alternative models in an attempt to develop the best characterization of transmission characteristics within a set of population.

Linkage analysis

Is a technique used to localize the gene for a trait to a specific chromosomal location. Scientists can follow a specific trait as it segregates through families of interest and determine if the trait appears to segregate with a known Genetic Polymorphism that has been localized to a specific chromosomal location. Linkage is often used as a first step to determine the approximate location of a gene of interest, permitting subsequent studies to identify the mutation responsible for a disease trait.

Association Studies are used to determine the allele of the gene associated with the disease.

MZ (monozygous) twins are genetically identical, and dizygous (DZ) twins are only as genetically similar as brothers and sisters would share approximately 50% of their genes in common. Discordance or differences in disease experience between MZ twins must be due to environmental factors and between DZ twins they could arise from both environmental and genetic differences. The difference in concordance between MZ and DZ twins for a particular phenotype can be used to estimate the effects of the extra shared genes in MZ twins, if the environment for twin pairs is the same. Studying disease presentation in twins is useful for differentiating the variations due to environment from those due to genetic factors and for estimating the amount of heredity in a phenotype. [1]

Complex traits such as bipolar disorder (Berrettini, 2000), obesity (Chagnon etal., 1998), and oral-facial clefting (Murray, 1995; Carinci etal., 2000), linkage analysis has produced either negative results or a plethora of weak, positive results that are not easily replicated, thus association studies which may be population-based and family-based standard case-control design are carried out. [12]

Genetics And Dental Caries

Diet and dental caries studies have revealed that variation in susceptibility to dental caries occurs even under identical and controlled environment. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes. Other predisposing factors include: The density or structural integrity of the dental Enamel, Topical and/or communal water fluoridation, composition of the secretions of the salivary glands, Nutrition and day-to-day dietary habits and Personal and professional oral hygiene. Inherited disorders of tooth development, salivary flow and immune system increase the incidence of dental caries. [18],[19][Table 3] represents Evidence for genetic contribution to dental caries through analysis of twins. [18]

Table 3: Evidence for genetic contribution to dental caries through analysis of twins

Fifty percentage of periodontitis susceptibility is attributed to heredity or genetic factors. The evidence is based on The study of inherited diseases and genetic syndromes, Familial studies, Twin studies and Population studies. [20],[21][Table 4] Represents Monogenetic and chromosomal defects associated with periodontal defects. [17]

Pioneering initial studies of the mode of inheritance of susceptibility to early onset periodontitis concluded that the increased prevalence in women, as well as the lack of father-to-son transmission in families indicated that susceptibility is inherited as an X-linked dominant trait. When the original pedigrees were analyzed redressing for ascertainment bias, they were found to be supportive of autosomal inheritance of early onset periodontitis. Evidence of attachment loss, pocket probing depth, gingival index, and plaque index has been confirmed by studies of identical twins reared together, fraternal twins reared together, and Identical twins reared apart. [20],[21]

Genetic Instability In Oral Cancer

It can be due to mutations in proto-oncogene (polymorphism in GST gene: GSTM1 and GSTT1 or CYP (cytochrome P450 ) or mutations in tumor suppressor gene (p16, 9p21, APC5q21-22 and p53) this may lead to loss of heterozygosity or failure to repair. [22]

In 1971, Dr. Alfred Knudson proposed the two-hit hypothesis. Knudson suggested that multiple "hits" to DNA were necessary to cause cancer. In the children with inherited retinoblastoma, the first insult was inherited in the DNA, and any second insult would rapidly lead to cancer. In noninherited retinoblastoma, two "hits" had to take place before a tumor could develop. This theory indirectly led to the identification of cancer-related genes. [23]

Foulkes etal. found first-degree relatives of patients with oral cancer have an RR of 3.5 times the general population and siblings had an RR of 8.6 for developing oral cancer. [24]

Prevalence of cleft lip and palate both in Caucasian population is 1:800-1000 while cleft lip alone is 1:1000. [25]

Incidence of cleft lip/ palate may be attributed to chromosomal disorders or they may be of multifactorial origin. Out of which 70% are non - syndromic while of 30% incidences are associated with Syndromes; which can be autosomal dominant, autosomal recessive oar X- linked. Sibling of the affected child is at a risk of 30 times more than the general population. [26] Syndromes associated with cleft lip and palate are represented in [Table 5].

Dental occlusion reflects the interplay between a number of factors including tooth size, arch size and shape, the number and arrangement of teeth, size and relationships of the jaws, and also the influences of the soft tissues including lips, cheeks and tongue. [8],[27][Table 6] is a compilation of studies done to determine the association between genetics and malocclusion. [27]

The first and for most are the health promotional measures which includes eugenics, euthenics, genetic counseling, and other genetic preventive measures like avoiding consanguineous marriages and late marriages secondly are the SPECIFIC protection against X-ray, ionizing radiations, and chemical mutagens. The preventive measure lies in early diagnosis treatment where genetic tests can be performed to know the underlying etiology and finally rehabilitation. [28],[29]

Recent Advances

0DNA vaccination

A direct injection of the plasmid DNA encoding antigenic proteins enables expression of the protein intracellular. This leads to a strong response involving both humoral and cellular immune system. [30]

Biochips

Biochips are also referred as DNA chips, usually helpful in drug discovery, pharmacogenomics, toxicological research, and toxicogenomics. [31]

Human cloning

It is used for mass production of animals engineered to carry human genes for the production of certain proteins that could be used as drugs and genetically modified organs that could be safely transplanted into humans. The perpetuation of endangered species, reproduction in infertile couples, production of offspring free of a potentially disease causing genetic flaw carried by one member of a couple. [32]

Recombinant DNA technology

This can be used in variable number tandem repeated in forensic medicine, this technology is helpful for gene therapy production of transgenic animals and plants and also recombinant drugs. [33]

Transcriptome analysis

The term used to describe the approach in which mRNA, and consequently gene expression, is analyzed in a biological sample under certain conditions at a given point in time. [34]

Proteomics

It aims to characterize all proteins in a biological sample at the functional level. [35]

Metabolomics

It is used to describe the quantitative analysis of all metabolites in a biological system such as cell, tissue, or biological fluid. [36]

Nutrigenomics

It aims to reveal the relationship between nutrition and the genome and to provide the scientific basis for improved public health through dietary means. [37]

Genetics In Prevention Of Periodontal Disease

Use of DNA probes helps to identify species-specific sequences of the nucleic acid that make up the DNA, thereby permitting the identification of the organism and gene replacement therapy is helpful in the correction of the genetic disorder. [38]

Genetics In Prevention Of Dental Caries

Genetic engineering in dental caries is the helpful production of transgenic strains of Streptococcusmutans which lack the specific gene required to produce decay. [39] Two residues within p1025 that contribute to binding (Q1025, E1037) were identified by site-directed mutagenesis. In an in vivo human streptococcal adhesion model, direct application of p1025 to the teeth prevented recolonization of S. mutans but not Actinomyces, as compared with a control peptide or saline. This novel antimicrobial strategy, applying competitive peptide inhibitors of adhesion, may be used against other microorganisms in which adhesins mediate colonization of mucosal surfaces. [14] Robert Buine (2000) has developed strains of S. mutans that are endowed with a gene to produce urease (urease enzymes of oral bacteria hydrolyze urea to ammonia, which can neutralize plaque acids). [20]

Public Health Significance

Globally, 7.6 million children are born every year with severe genetic or congenital malformations. The genetic and congenital disorder is the second most common cause of infant and childhood mortality and occurs with a prevalence of 25-60/1000 births. [40]

Epidemiology of public health practice by Friis

Genetic disorders are perceived as less important than other public health problems. In poorer countries, neonatal and infant mortality is mostly due to infectious diseases and lack of antenatal care, so genetic diseases are not perceived as having enough importance for governments to allocate resources to establish genetic services as is perceived as extremely expensive and inaccessible by people.

There is a lack of knowledge regarding genetic diseases and its prevention among the general population. An important premise is that a better understanding of the genetic etiology of the diseases can facilitate early detection in high risk subjects. Once high risk groups are identified we need to create awareness in them and educate those regarding genetic diseases. It also helps in designing of more effective intervention strategies. Exciting new technology based on the foundation of genetic research has the potential to further enhance the quality of life. [41]

Khoury grouped the range of activities into categories that includes assessment of the impact of the genes and their interactions with the modifiable disease risk factors on the health status of the population to be undertaken, development of policies as to when and how genetic tests are to be applied in disuse prevention programs and development public health genetic programs should be effective and of the highest quality. [42]

The government should be appraised to develop cost-effective genetic counseling techniques and genetic therapy that is affordable by the community. Progress in the field will require training of a new generation of the scientists with requisite skills, as well as greater collaboration and interdisciplinary work.

Conclusions

The traditional epidemiologic approach has proved useful for generating hypotheses and unraveling disease etiologies. But now it is possible to go beyond these methods and look inside the "black box" of the disease process which would be able to change the definition of the risk factors or clarify their location in the casual model. The control of genetic diseases should be based on an integrated and comprehensive strategy combining best possible treatment and prevention through community education, population screening, genetic counseling, and the availability of early diagnosis.

Foulkes WD, Brunet JS, Kowalski LP, Narod SA, Franco EL. Family history of cancer is a risk factor for squamous cell carcinoma of the head and neck in Brazil: A case-control study. Int J Cancer 1995;63:769-73.